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Development of regenerative therapy of central nervous system, using with asialo-erythropoietin

使用脱唾液酸促红细胞生成素开发中枢神经系统再生疗法

基本信息

批准号：
20791020
负责人：
MIKI Yoshihito
金额：
$ 2.58万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2011
项目状态：
已结题

项目摘要

Systemic administration of high-dose recombinant human erythropoietin(rhEPO) is known to attenuate ischemic injury. However, high-dose rhEPO might aggravate ischemic lesions by increasing blood viscosity because of its erythropoietic effects. Asialoerythropoietin(asialoEPO), an EPO derivative with an extremely short plasma half-life, has considerably lesser erythropoietic effect than that of naive EPO. We attempted to determine whether asialoEPO exerts the same neuroprotective effect as naive EPO in a gerbil transient forebrain ischemia model, and resulting multiple dosing of asialoEPO, like EPO, could protect the hippocampal CA1 neurons from ischemic damage without affecting erythropoiesis. This data suggested that asialoEPO would be novel neuro-protective agent in the future.

已知全身给予高剂量重组人促红细胞生成素（rhEPO）可减轻缺血性损伤。然而，大剂量rhEPO由于其促红细胞生成作用，可能通过增加血液粘度而加重缺血性病变。脱唾液酸促红细胞生成素（asialoEPO）是一种血浆半衰期极短的EPO衍生物，其促红细胞生成作用明显低于天然EPO。我们试图确定在沙鼠短暂前脑缺血模型中，去唾液酸EPO是否发挥与初始EPO相同的神经保护作用，并且由此产生的多次给药的去唾液酸EPO，如EPO，可以保护海马CA1区神经元免受缺血性损伤而不影响红细胞生成。提示去唾液酸促红细胞生成素有望成为一种新型的神经保护剂。